Do imitations of anti-VEGF medicines (biosimilars) work as well as the original anti-VEGF medicines for people with neovascular age-related macular degeneration (nAMD)?

Key messages

• Imitations (biosimilars) of anti-vascular endothelial growth factors (anti-VEGFs) work as well as the original anti-VEGF medicines when used to treat neovascular age-related macular degeneration (nAMD) for up to a year.

• Anti-VEGF biosimilars cause similar unwanted effects to the original anti-VEGF medicines for up to a year.

• Future research should take place over more than one year to understand the desired and unwanted effects of anti-VEGF biosimilars on vision and vision-related well-being.

What is neovascular age-related macular degeneration (nAMD)?

Neovascular age-related macular degeneration (nAMD), also called ‘wet’ AMD, is a serious eye condition that causes partial or complete vision loss. It affects millions of people worldwide. It is caused when new blood vessels grow under the macula, which is an area under the retina at the back of the eye. The blood vessels leak fluid, which damages the macula and so leads to loss of vision.

How is nAMD treated?

nAMD is treated with medicines called anti-vascular endothelial growth factors (anti-VEGFs), which stop the growth of the abnormal blood vessels under the retina. People with nAMD receive regular injections of anti-VEGFs directly into their eyes. So far, 5 different anti-VEGF medicines have been approved to treat nAMD. These medicines have been shown to stop further damage to the retina and so help to protect people’s remaining vision.

Anti-VEGF medicines are expensive and injections are usually needed every month. The injections can cause unwanted effects such as bleeding and inflammation of the eye. A small number of people develop antibodies that stop these medicines from working.

What are biosimilars?

Anti-VEGF biosimilars are newly developed versions of the original anti-VEGF medicines; they are similar but not exactly the same as the original medicines. Since biosimilar medicines do not have exactly the same structure as the original medicines, it is possible that they do not produce exactly the same effects as the original anti-VEGF medicines. These biosimilars are injected in the same way as the original anti-VEGF medicines, and are cheaper than them.

What did we want to find out?

We wanted to find out whether anti-VEGF biosimilars work as well as the original anti-VEGF medicines at preventing further loss of vision in people with nAMD. We also wanted to find out whether anti-VEGF biosimilars cause similar unwanted effects to the original anti-VEGF medicines.

What did we do?

We searched for studies that compared anti-VEGF biosimilars with the original anti-VEGF medicines. We compared and summarized the results of these studies and rated our confidence in the evidence based on factors such as study method and size.

What did we find?

We found nine studies that involved 3814 people (3814 eyes) with nAMD. Five studies enrolled people from different countries in Europe, North America, and Asia. Two studies took place in India, one study was conducted in Japan and one in South Korea. All the studies were funded by the pharmaceutical companies that developed the anti-VEGF biosimilars. The studies compared two of the original anti-VEGF medicines, ranibizumab and aflibercept, to a number of biosimilars designed to mimic them. The studies lasted from 12 to 52 weeks.

The studies showed little to no difference between anti-VEGF biosimilars and the original anti-VEGF medicines for the prevention of further loss of vision in people with nAMD.

There was probably little to no difference between anti-VEGF biosimilars and the original anti-VEGF medicines for:

• vision-related wellbeing;

• serious eye-related unwanted events (these affected approximately 12 to 14 people out of 1000 treated); and

• treatment-related unwanted events that resulted in death or people stopping treatment (these affected between 24 and 25 people out of 1000 treated).

There may be little to no difference between anti-VEGF biosimilars and the original anti-VEGF medicines for the:

• production of antibodies that stop these medicines from working (antibodies appeared in between 44 to 53 people out of 1000 treated); and

• the concentration of medicine in the blood (mean maximum serum concentration). (This means that the anti-VEGF biosimilars are present in the body at similar levels to the original anti-VEGF medicines, and so may be expected to work for the same length of time between doses.)

What are the limitations of the evidence?

We are highly or moderately confident in our findings regarding prevention of further vision loss.

We are less confident in our results for:

• unwanted events, as these did not happen often within the time frame of the studies;

• vision-related wellbeing, and mean maximum serum concentrations as these were reported in only two studies; and

• production of antibodies against anti-VEGF biosimilars and the original anti-VEGF medicines, as so few people produced them.

How up to date is this evidence?

The evidence is current to June 2023.